This application is entitled to the benefit of, claims priority from, and incorporates by reference subject matter disclosed in UK Patent Application No. 0021976.6, filed on Sep. 7, 2000.
This invention relates to fiber optic probes and sensors, particularly but not exclusively for invasive medical applications used in the measurement of at least one parameter within the body. These parameters (measurands) include pressure, differential pressure, radiation, fluid flow, temperature, and biological parameters such as concentration of particular chemical and biological substances at one or a number of measuring locations within the body. The invention also extends to methods of medical treatment and diagnosis which employ the fiber optic probes of the invention. Whilst some aspects of the invention relate to invasive medical applications, features and aspects of the probes may also find application in other measuring contexts, such as ex-vivo or in vitro medical uses.
With the advance of technology relating to medical diagnosis and therapy there is an on-going need to improve methods and systems for sensing various physical, chemical and biological parameters within the body. Such sensing is needed both during diagnosis and during treatment. Further, there is increasing emphasis on the use of minimally invasive medical techniques, intended to reduce the trauma to the patient during and following medical procedures. In this respect, given their small dimensions, fiber optic devices are commonly used in various aspects of medicine, for example for viewing a treatment site via an endoscope, for delivery of laser therapy within the body, and in the context of optical biochemical sensor probes for monitoring and measuring various parameters.
A variety of prior art biochemical sensors for medical use are known, and they generally include a coating or reagent provided on the end face of a waveguide provided at or defined by the end of an optical fiber. The coating or reagent material reacts with interrogating light in order to provide a change in optical response of the detector. The sensing mechanisms may be chemical systems whose spectra change under the effect of particular reactions, or dielectrics which change refractive index through induced swelling or another mechanism.
These known sensors operate through direct interaction between the reactant coating and the interrogating light, which leads to certain practical disadvantages, and are generally configured to be responsive to only a single parameter within the body to be measured, for example a particular chemical or biological substance. It is an object of the invention to provide an improved fiber optic sensor probe for invasive medical use.
A first aspect of the invention provides a body compatible fiber optic sensor probe for invasive medical use, such probe including at least one optical fiber, the fiber or fibers having at least one sensing region adapted and arranged such that the probe has simultaneously measurable respective optical properties responsive to respective different parameters within the body, such properties being dependent upon mechanical strain established in the fiber or fibers in response to said parameters.
Preferably, the sensing region comprises a mass of reactive material configured to create mechanical strain within the fibre in such a way as to change its optical response.
Preferably, the probe enables the simultaneous measurement and quantification of two or more different parameters in use. Alternatively, only a first parameter may be measured and quantified, with the measurement of a second parameter being used to correct the measurement of the first parameter in relation to variations in optical properties caused by the second parameter which might otherwise interfere with the measurement and quantification of the first parameter.
Such a probe represents a new departure from known medical fiber optic probes in that more than one parameter can be measured simultaneously by a single probe in a design of probe in which the detectable optical properties are dependent on strain established in the fiber or fibers. In such a probe there need be no direct interaction between the interrogating light and a reactant material as is the case with most prior art medical probes. These parameters or measurands include pressure, radiation, fluid flow, temperature, and biological parameters such as antibodies, pathogens etc., and/or chemical parameters such as dissolved blood gases, electrolytes, glucose etc.
A medical probe according to the invention preferably has one optical property which changes in accordance with a first parameter, and a further, different optical property which changes in accordance with a second parameter, such that through the use of a suitable interrogation system each parameter can be measured independently.
The invention extends to sterile probes of the type described above and below, and to sterile packs including such probes.
The invention also provides methods of treatment or diagnosis of the human or animal body using any of the probes described herein.
Viewed from a further aspect the invention provides a method of treatment or diagnosis of a human or animal body, which involves the simultaneous sensing of different parameters within the body through the use a fiber optic probe having a sensing region or regions with measurable optical properties dependent on mechanical strain established in one or more optical fibers wherein the probe is responsive to at least two different parameters within the body. Preferably, two or more parameters are simultaneously measured and quantified.
Various general configurations of probe design in accordance with the invention are envisaged. In one set of embodiments the probe comprises a tubular housing, which contains therewithin a portion of the or each optical fiber, and is arranged such that the fiber, in the sensing region(s) thereof, is exposed to the parameter to be measured.
In a preferred such embodiment the probe consists of two or more fibers arranged side-by-side within the housing, these fibers having respective sensing regions which are responsive to different parameters or measurands. Such an arrangement represents a new departure from known fiber optic sensors.
Viewed from another aspect, therefore, the invention provides a fiber optic sensor device, which comprises a housing mounting therewithin at least two optical fibers mounted side-by-side, these fibers including respective sensing regions responsive primarily to respective different parameters to be measured.
As discussed below, the housing is constructed such that the fibers are suitably exposed to the different measurands in the sensing regions thereof.
Additionally or alternatively, one or more fibers can be provided with sensing regions responsive primarily to different parameters at axially spaced locations along the fiber length. In such a probe, only a single optical fiber needs to be provided, though multiple fiber probes are also possible, with each fiber having multiple sensing regions.
A further aspect of the invention therefore provides a body compatible fiber optic sensor probe for invasive medical use, such a probe including at least one optical fiber having axially spaced sensing regions, these regions providing in use distinguishable optical responses or outputs dependent primarily on different parameters within the body.
In such an embodiment, the optical fiber or fibers may again be located in a suitable, body compatible protective housing.
In certain embodiments of the invention, one of the parameters to be detected is fluid pressure within the body. In such an arrangement, an optical fiber is configured in at least one sensing region to provide a changing optical property depending on the pressure applied to the fiber. Optical fiber pressure sensors are known in other contexts, as will be described below.
In a preferred embodiment of the invention in which the fiber or fibers of the probe are mounted within a protective tubular housing, such housing may be filled with a liquid or gel such that external pressure applied to the probe housing is transmitted to the surface of a pressure sensitive region of the optical fiber within the housing. In one such embodiment, the protective housing includes an aperture or apertures covered by a flexible membrane, through which external pressure is transmitted to the liquid or gel contained within the housing and thereby is applied to the optical fiber. The use of a gel or liquid interposed between the or each fiber and the probe outer housing is advantageous in that, as well as pressure, other physical, biological or chemical parameters to be measured can be transferred to sensing regions of the fiber or fibers within the housing.
For example, a particular embodiment of the invention includes a temperature sensing region as well as a pressure sensing region within one or more optical fibers. Through the use of a liquid having good thermal conductivity, it will be appreciated that both pressure and temperature can be transferred from the environment outside the probe housing to the or each optical fiber within the housing via the liquid contained therein. In this embodiment, the probe housing, as well as including a pressure translating membrane, should be formed of a material of good thermal conductivity.
Further, in the case of a biological or chemical sensor, a liquid or gel within the housing provides a convenient means whereby particular molecules to be sensed can diffuse through the liquid and thereby be transferred to one or more optical fibers located within the housing, such fiber(s) having a suitable reactive sensing element coupled to the fiber whereby a change in optical response is obtained.
A further aspect of the invention provides an optical fiber sensor device which includes a sealed tubular housing containing therewithin at least one optical fiber having at least one sensing region, there being a liquid or flowable gel disposed within the housing and surrounding the fiber, the liquid or gel permitting the transfer of at least one parameter to be measured from a region outside the housing to a sensing region of the fiber.
As discussed, the or each parameter transferred by the liquid can be any of pressure, temperature, or biological or chemical substances which can diffuse through the liquid or gel.
A suitable liquid is isotonic saline.
The housing may include one or more apertures covered by a membrane, the membrane allowing the application of pressure to the liquid or gel from the surrounding environment and/or allowing the selective diffusion of molecules to be sensed through the membrane.
In a multi-parameter sensitive probe according to the invention, the probe has changeable and detectable respective optical properties responsive to different parameters. These “respective optical properties” can in fact be the same general fiber property, but provided in different fibers of the probe which are configured to render the properties responsive to different parameters.
Hence, the optical output from two fibers may be generally the same, but the variation in these outputs would vary differently in response to different measurands.
In preferred embodiments of the invention, however, different and distinguishable optical properties of a particular fiber, or of respective fibers, are responsive, at least primarily, to respective parameters to be measured. This enables the more convenient use of a single fiber for measurement of different parameters through the use of differently responsive sensing regions. These different optical properties can, for example, be spectral peaks or troughs at different wavelengths, whose respective wavelength shifts are responsive to different parameters within the body.
In a particularly preferred embodiment, one optical property of the sensor probe is the absolute wavelength of one or more spectral peaks of the fiber's optical response, and a further optical property is the spacing between spectral peaks or troughs in the mutually orthogonal polarization planes of the fiber. Through the use of suitably calibrated and known interrogation means, these properties can be measured independently and, according the invention, are preferably primarily responsive to different body parameters.
The required optical properties of the fiber at the or each sensing location can be provided by various known methods. For example, the sensing regions of the fiber may be configured to provide a form of “Fabry-Perot” (F-P) interferometer, whose output wavelength when interrogated by a suitable light source depends on longitudinal stress applied to the fiber. In such a system there are in effect spaced “mirrors” within the fiber whose spacing determines the output wavelength which therefore changes with longitudinal strain within the fiber.
Alternatively, the sensing regions can be based on active or passive fiber Bragg gratings (FBG's) written into the optical fiber core. These gratings are made by producing periodic variations in the refractive index along a short section in the core of an optical fiber, and methods for fabricating such gratings are generally known in the art. Passive FBG devices, and interrogating systems therefor, are known for example from U.S. Pat. No. 5,828,059 and WO 98/36252. In U.S. Pat. No. 5,828,059, a fiber is adapted to sense both radial pressure and longitudinal strain. The radial pressure is sensed through the use of an FBG in the region of a fiber provided with side air holes either side of the core. Radial stress applied to such a fiber will cause a change in the birefringence of the fiber and a detectable change in the spacing between the spectral peaks of the reflected light in mutually orthogonal polarization planes. The absolute wavelength of the peaks depends on the grating spacing, and is therefore responsive to temperature, which causes longitudinal contraction/expansion of the fiber. The change in birefringence is less sensitive to temperature changes. Hence, such a sensing arrangement is particularly suitable for use in a medical probe according to the invention used for multi-parameter measurements.
A further preferred sensing method used for the probes of the present invention involves the use of active fiber lasers, particularly active FBG lasers. Such devices for use in fiber optic sensors are described, for example, in U.S. Pat. No. 5,844,927 and U.S. Pat. No. 5,564,832. In such systems, an end-pumped fiber laser with distributed feedback (DFB) oscillates on two orthogonally polarized wavelengths. Again, the distance between these wavelengths may be tuned by changing the birefringence of a fiber, and therefore can be pressure sensitive. The absolute wavelength of each peak is responsive to longitudinal strain, and hence is responsive to temperature, for example. The aforementioned prior art references each describe suitable interrogation systems for detecting fiber outputs which are suitable for use in the present invention. These involve suitable laser light sources, and spectral analysis systems of generally known types.
In embodiments of the invention, a DFB laser, consisting of a single FBG written into a rare-earth doped optical fiber, can be used. Alternatively, a fiber DBR (distributed Bragg Reflector) laser can be used. As is well known, these fiber lasers are pumped from one end by a semi-conductor laser, and oscillate to provide the detectable optical properties or output of the sensor. The distal end of the fiber is generally terminated at a cleaved end to prevent back reflections at the fiber laser wavelength, and may also be provided with a suitable pump reflector, such as a passive FBG at the pump wavelength to prevent residual pump light exiting from the fiber end, which could cause heating.
Optical fiber probes according to the invention can incorporate one or more of the above optical systems whereby the changeable optical properties responsive primarily to different parameters are obtained.
The fiber sensing regions can be rendered responsive to various parameters by different means. In a preferred embodiment, at least one sensing region comprises a sensing element formed of a material which undergoes a change in volume upon exposure to a parameter to be measured, such change in volume creating a strain within the fiber whereby a detectable change in optical response is obtained.
In those embodiments discussed above including a passive or active fiber Bragg grating in a birefringent fiber, the sensing element may cause longitudinal strain, bonding strain, and/or generally radially directed strain, so that there is a change both in the absolute wavelength of the optical response or output of the fiber, and a change in the distance between the spectral peaks in mutually orthogonal polarization planes.
A particularly convenient form of sensing element is in the form of a coating of reactive material provided on the fiber. Such a coating may be configured to apply longitudinal and/or radial strain upon swelling when exposed to a measurand.
A birefringent fiber may be a side-hole fiber, a D-fiber, a Bow-Tie fiber, or a Panda fiber, or another fiber with special geometry which establishes a change in birefringence upon sideways pressure.
It is also possible to provide the sensing element in one or more side-holes of the fiber, such that when exposed to a measurand, the element swells and causes distortion of the fiber and establishes a change in birefringence.
Alternative forms of sensing element include, for example, suitable piston and cylinder arrangements, in which a sensing element expands to provide a longitudinal strain within the fiber which in turn changes the detectable optical response. These and other possible probe arrangements are described in our co-pending patent application entitled “Fiber Optic Probes” lodged simultaneously herewith.
Where one or more fiber sensing regions of a probe according to the invention is provided with a sensing element arranged to create mechanical strain in the fiber and alter its optical properties, the sensing element can comprise a variety of materials depending on the measurand to be detected. The reactive material consists of or is provided with an indicator which indicates the presence of the measurand and determines its concentration (in the case of a chemical/biological sensor) or magnitude (in the case of a pressure, radiation or temperature sensor). The material should be highly sensitive in that it should undergo a large volume change for relatively low concentrations or magnitudes of the parameter to be measured, so that a strain is applied to the fiber creating a readily detectable change in optical response.
Preferred reactive materials may be reactive to non-ionizing radiation, ionizing radiation and chemical or biological, including immunological, interactions.
In certain embodiments of the invention, the reactive material of the sensing element is immobilized on a solid support medium, such as a polymer, copolymer, or various glasses. The immobilization method can be mechanical, electrostatic or chemical. The support medium can remain inert to the reaction being analysed, although in some embodiments it is envisaged that the support could also itself act as a selective element, for example through controlled porosity, to enhance the selectivity of the sensor, and to protect the active medium of the sensor element.
In other embodiments of the invention, for example where the sensing element is located in a cylinder, or within the side-holes of a fiber, it is envisaged that the reactive material of the sensing element could be dispersed or immobilized in a fluid or gel, which swells or contracts in response to a target measurand in order to apply the required stress to the fiber.
In all cases, a separate body compatible membrane covering or enclosing the sensing element can be provided to enhance selectivity of the sensor and protect the active part of the sensor. This membrane can provide selectivity based on size selectivity of the measurand species through controlled porosity of the membrane, chemical/biochemical selectivity through chemical reactions, or ionic selectivity through electrostatic interactions.
In the case of the coating embodiments, the coating can conveniently be made from a form of paint or bonding material, a polymer gel material, or from a porous material, such as a sol-gel glass or ceramics, to make an open matrix configuration. A further example of a suitable material for use as the sensor is micro-spherical balls, with additives to generate chemical selectivity for a selected group of molecules. Such balls can be confined, for example, within a piston and cylinder, or within a membrane.
One preferred sensing element comprises ionic N-Isopropylacrylamide (NIPA) polymer gel copolymerised by sodium acrylate (SA) which is known to exhibit substantial swelling in an ionic solution. This swelling is a result of an increased osmotic pressure within the gel due to mobile counter ions to the bound cations. As described, for example, in U.S. Pat. No. 5,744,794, hydrogel materials can be formulated of numerous other types and consistencies, and can be prepared to respond to different external stimulii. Those skilled in the art will recognise that hydrogel materials can be formulated to respond to a variety of in body parameters and therefore are particularly suited for use in the sensor probes of the present invention.
The swelling behaviour of polymer gel networks is governed not only by the affinity of polymer chains for solvents, as in the NIPA-SA gel example, but also by the cross-linking density, (see for example M. Shibayama and T. Tanaka, “Volume phase transitions and related phenomena of polymer gels,” in Advances in Polymer Science, vol. 109, Springer Verlag, 1993). The cross-linking density controls the elastic restoring force. Affecting the elastic restoring force in turn affects the equilibrium swelling volume of the gel network.
Polymer gel networks responsive to specific biochemicals can therefore also be prepared by application of stimuli-sensitive complex formation at cross-linking points in the gel network, e.g. application of antigen-antibody binding at cross-linking points.
One way to synthesize such materials is to use the well-known polyacrylamide gel system (PAAm) and including the functionalized recognition molecule in the cross-link-co-polymerization reaction. An example of this is described by T Miyata et al., “A reversibly antigen-responsive hydrogel,” Nature, vol. 399, pp.766-769, 1999, who used the polyacrylamide gel system to conjugate IgG antibody to prepare an antigen-responsive gel. More specifically they used rabbit immunoglobulin G (rabbit IgG) and goat anti-rabbit IgG (GAR IgG) as the antigen and antibody. Competitive binding of the free antigen (analyte) break the antigen-antibody (receptor) cross-link, thereby reducing the cross-linking density and triggering a change in gel volume.
There are numerous other antigen-antibody or other specific biochemical “key-lock” pairs that can be selected for such biochemical sensitive polymer gel networks, e.g. biotin-avidin and various lectin-saccharide pairs. Any of these can be used to provide the sensing elements of the present invention.
In a preferred embodiment of multi-parameter detecting probe, the probe consists of a tubular housing mounting therewithin in side-by-side arrangement two or more optical fibers, at least one of such fibers being provided with a sensing element responsive to a first parameter to be measured, and another fiber being absent such sensing element, or provided with a different sensing element to detect a different parameter.
Where the second fiber is absent the sensing element, the optical response from this fiber may be used to correct the output from the fiber provided with the sensing element for changes in temperature, for example, which might otherwise interfere with the accurate measurement of a chemical of physical parameter detected by the sensing element.
Viewed from a further aspect, the invention provides a fiber optic sensor device comprising a tubular housing mounting therewith optical fibers in side-by-side relation, a first fiber providing a birefringent response dependent on pressure applied to the fiber, and the second fiber providing a temperature dependent response which may be used to correct measurements based on the optical output of the first fiber.
The pressure responsive fiber may be provided in the or each sensing region thereof with a reactive coating as described above, which swells in response to a particular measurand. Alternatively or additionally, a pressure responsive fiber may be arranged to be responsive to the pressure outside the probe.
A further embodiment of the invention includes three fibers extending along a probe housing. A first fiber has at least one pressure sensitive region provided with a reactive coating; a second fiber has at least one pressure sensitive region but not provided with the reactive coating; and the third fiber is responsive only to longitudinal strain. The fibers each have like FBGs or other sensors, in their sensing regions. In this way, a single probe may be used to measure, for example, chemical or biochemical parameters, pressure, and temperature. Further, the output from the temperature sensor may be used to correct the measurements of the other two parameters.
In such multiple fiber arrangements, the distal ends of the fibers can be connected via a fiber minibend device, such as described in U.S. Pat. No. 5,452,393, which couples light between the fibers. In this way, pumping light may be passed only through one fiber, and is reflected at the free end so as to be passed through lasers in both fibers (where the detecting system comprises active fiber lasers).
In all embodiments of the invention, several sensing regions can be placed in series along one or multiple fibers for distributed measurements, in which case the detecting systems along the same fiber should have non-overlapping wavelengths. The outputs from these can be multiplexed using known means.
Viewed from a further aspect the invention provides a fiber optic sensor device, comprising a fiber or fibers having respective sensing regions located within a sealed tubular housing containing a liquid interposed between the sensing regions and the wall of the housing, a first sensing region being primarily pressure dependent, and a second sensing region being primarily temperature dependent.